WO2017129802A1 - Collecteur de fraction liquide pour système de chromatographie en phase liquide - Google Patents

Collecteur de fraction liquide pour système de chromatographie en phase liquide Download PDF

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Publication number
WO2017129802A1
WO2017129802A1 PCT/EP2017/051867 EP2017051867W WO2017129802A1 WO 2017129802 A1 WO2017129802 A1 WO 2017129802A1 EP 2017051867 W EP2017051867 W EP 2017051867W WO 2017129802 A1 WO2017129802 A1 WO 2017129802A1
Authority
WO
WIPO (PCT)
Prior art keywords
arm
fraction collector
receptacles
carriage
dispenser
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2017/051867
Other languages
English (en)
Inventor
Stefan DARGY
Olle Bjernulf
Mats Lundkvist
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Global Life Sciences Solutions USA LLC
Original Assignee
GE Healthcare Bio Sciences Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GE Healthcare Bio Sciences Corp filed Critical GE Healthcare Bio Sciences Corp
Priority to US16/070,846 priority Critical patent/US11333641B2/en
Priority to CN201780008928.6A priority patent/CN108496077B/zh
Priority to EP17701875.1A priority patent/EP3408663B1/fr
Priority to JP2018539405A priority patent/JP7111615B2/ja
Publication of WO2017129802A1 publication Critical patent/WO2017129802A1/fr
Anticipated expiration legal-status Critical
Priority to US17/727,375 priority patent/US11686712B2/en
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/80—Fraction collectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1011—Control of the position or alignment of the transfer device
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0439—Rotary sample carriers, i.e. carousels

Definitions

  • the present invention relates to fraction collectors, for example fraction collectors used in the field of liquid chromatography for sequential dispensing of liquids from a source, typically collected fraction by fraction in a plurality of adjacent receptacles in a cassette or cassettes over a time period as the chromatography process progresses.
  • a fraction collector is a device used for dispensing a liquid into a number of receptacles. Traditionally receptacles such as test tubes are fed towards a dispensing means one by one, for example on a conveyor or track.
  • fraction collectors including a rotatably mounted turntable for supporting a plurality of collection tubes, for example U.S. Pat. No. 4,862,932 and U.S. Pat. No. 6,450,218.
  • a liquid is sequentially discharged into the collection tubes through an outlet conduit, such as a hollow needle.
  • the outlet conduit is mounted on an arm reaching over the turntable.
  • the arm can swing around a vertical post to be positioned over different radial rows of collecting tubes.
  • microplates in an eight by twelve, two dimensional orthogonal array. Such plates typically have dimensions of about 85mm by 128mm, thus, taking into account the thickness of the plastics moulded well walls, each well has an opening of about 8mm across. The height of the wells can be about 45mm. If the wells are deep enough, a millilitre or so (lml-1.5ml), of fluid can be collected in each well.
  • a conventional X-Y-collector has a table for holding the receptacles, and is further equipped with means for moving a dispensing tube over and between the receptacles.
  • the moving of the dispensing tube is achieved by the use of a set of stepping motors.
  • these X-Y machines take up a relatively large area on the bench because, the linear drives needed for an X-Y collector occupy more volume than a rotary drive so tend to take up more space on the laboratory bench. Even when the receptacle table is moved in the X and Y directions, and the dispensing head is kept stationary, further valuable bench-space is lost.
  • the turntable fraction collector is useful in many applications and is generally more space efficient because the rotational drives take up less space than linear drives needed for X-Y collectors.
  • X-Y-collectors are more suitable when handling a large number of receptacles formed in microplates, because they can operate in the same linear directions as the microplate array.
  • Conventional turntable fraction collectors cannot handle such microplates.
  • a X-Y-collector Compared to the turntable collector, a X-Y-collector requires a longer attachment tubing, since the equipment providing the liquid is stationary with respect to the receptacles, and the tubing therefore has to follow the dispensing tube to any receptacle.
  • this long tubing is a disadvantage because the long travelling distance of the liquids in the tube gives the initially separated components in the liquid a longer time period to diffuse within the liquid flow, and consequently the precision of the separation is negatively affected.
  • Embodiments of the invention described herein address the need for a space saving fraction collector with the ability to dispense into a microplate formed as a two dimensional array of closely spaced wells.
  • Embodiments of the invention described herein address the need for a reliable and rugged, yet small fraction collector.
  • Embodiments of the invention described herein address the need for a low cost fraction collector.
  • the invention provides a fraction collector according to claims 1 and 10 having preferred features defined by claims dependent on claims 1 and 10 respectively.
  • An embodiment of the fraction collector according to the invention includes a table for supporting a liquid receiving plate including a two dimensional array of liquid receptacles, an arm rotatably mounted for movement above the table and a carriage supported on the arm for linear movement relative to the arm, said carriage supporting a liquid dispenser adapted for dispensing liquids movable in a two dimensional plane above the table for dispensing liquids into said receptacles.
  • the embodiment of the traction collector mentioned immediately above includes a first drive motor operative to rotate the arm , and a second drive motor operative to move the carriage, each drive motor being located under the table.
  • Figure 1 shows a perspective view of an embodiment of a fraction collector according to the present invention
  • Figure 2 shows a further perspective view of the fraction collector shown in Figure 1 ;
  • Figures 3,4 &5 each show a plan view of the collector shown in Figure 1 , with the motions of the parts superimposed.
  • Figure 6 shows a perspective sectional view of the fraction collector shown in Figure 1;
  • Figure 7 shows details of an arm component of the fraction collector shown in Figure 1 ;
  • Figure 8 shows a schematic representation of the sectional view shown in Figure 6;
  • Figure 9 shows a perspective view of another embodiment of the invention; and
  • Figure 10 shows a sectional view through the middle of the embodiment shown in Figure 9.
  • the fraction collector 10 includes a hollow base 20 having a table top 22 for receiving two microplates PI and P2 and a static pedestal 40 extending upwardly from the table so as to be between the two plates, which in turn supports an arm 30, rotatable on the pedestal 40 and above the microplates PI and P2.
  • the pedestal 40 thus sits mid-way along the width of the table and to one side of the table, allowing two microplates to sit on the table, one on each opposing side of the table/pedestal.
  • the arm 30 supports a repositionable carriage 34 which in turn supports a liquid dispenser 35 above the microplates.
  • the dispenser 35 is positionable above any one of a plurality of liquid receptacles, herein called wells, Wl and W2 of the microplates PI and P2 for dispensing liquids into those wells.
  • the dispenser 35 is fed by a flexible tube 36 shown only partially, supplied, in this embodiment, by chromatographic equipment 100.
  • Figure 2 shows the same collector 10, and also shows a bottom plate 24 which, together with the unitarily moulded housing 20 and pedestal 40, provides protection against liquid ingress into the housing, particularly if liquid is spilled onto the table 22.
  • Figure 3 shows the swinging motion attainable by the rotation of the arm 30.
  • Arrow R represents the arcuate movement of the arm 30 about centre of rotation defined by axis C which is perpendicular to the table 22.
  • the dispenser 35 can be positioned in any position in the arc.
  • Figure 4 shows the further generally linear motion attainable by movement of the dispenser along the arm 30 in the direction of arrow L.
  • the linear movement in the direction of arrow L occurs in use preferably concurrently with the arcuate moment described above, but sequential movement is possible also.
  • the dispenser 35 is positionable and repositionable over any one of the wells Wl or W2, for dispensing liquid into those wells.
  • the arm may swing through 360 degrees as shown in Figure 5.
  • a further microplate P3 can be mounted to the extension 22' and can be used to collect further fractions of liquid if needed.
  • the slight disadvantage of this embodiment is that further bench space would be needed.
  • Figures 6, 7 and 8 illustrate the mechanisms used to obtain he desired dispenser movements.
  • Figure 6 is a section of the collector housing 20 taken along the plane IV-IV in Figure 4, but with the arm 30 positioned over the sectional plane IV-IV so that its internal features can be better viewed in Figure 6.
  • the arm 30 includes a rigid arm member 31 supporting the carriage 34 which holds the dispenser 35 (Figure 1).
  • the carriage 34 extends into a slot 31a in the arm member 31 , and the dispenser 35 will be attached to the lower end of the carriage protruding from the slot 31a.
  • the arm member 31 is mounted on a support cylinder 42 which is driven to rotate by a predetermined angle about centre line C as described more fully below to cause arcuate movement of the arm 30 at least about arc R ( Figure 3).
  • FIG. 7 shows the arm 30 with the cover 32 removed, revealing the arm member 31 mounted to the cylinder 42 for rotational movement about axis C.
  • Fixed to the top of the drive shaft 38 is a toothed upper carriage drive pulley 33, which can rotate independently of the arm member 31.
  • the carriage drive pulley 33 in use translates a toothed carriage drive belt 38a.
  • the carriage belt 38a is held taught by an additional arm pulley 37 at the distal end of the arm member 31 and by a tensioner pulley 33a acting on the outside face of the belt 38b between the two pulleys 33 and 37.
  • the carriage 34 is mounted on a linear bearing 39 mounted to the arm member 31 , and is attached to the carriage belt 38a, such that movement of the carriage belt 38a via a drive pulley 33 and a drive shaft 38 causes linear movement of the carriage 34 along the bearing 39 in the direction of arrow L ( Figure 4), and so the position of the carriage 34 and the dispenser 35 can be changed.
  • Figure 8 shows more details of the mechanisms, in schematic form.
  • Drive shaft 38 can be rotated by means of a toothed lower carriage drive pulley 52 connected to a stepper motor 53 via a further carriage drive belt 54.
  • the stepper motor 53 has an output pulley 53a which can be smaller than the drive pullet 52 to provide slower but more accurate carriage movements if needed, although other ratios, for example a 1 :1 ratio as shown in Figure 6, could be employed.
  • the rotation of the whole arm 30 is brought about by rotation of an arm pulley 55, driven by a toothed belt 57 in turn driven by the output pulley 56a of an arm driving stepper motor 56.
  • the output pulley 56a is smaller than the driven pulley 55 to reduce speed and increase accuracy, but other ratios could be used, for example a 1 :1 ratio as shown in Figure 6.
  • Electrical parts including the drive stepper motors 53 and 54 together with known stepper motor control electronics 27, are enclosed within the housing 20 in the space 26 under the table 22, closed by the base plate 24. This not only provides a compact arrangement, but also inhibits liquid ingress into the electrical parts.
  • microplates PI and P2 for example, are mounted to the table 22 in complementary register slots, or channels 60 which match the features on the underside of the microplates PI and P2.
  • the control electronics is used to control the stepper motors such that the dispenser, translates signals supplied by the chromatographic equipment into the stepper motor signals needed to position the dispenser 35 sequentially above the known positions of the wells of a respective microplate by movement of the dispenser 35 in a two dimensional plane over the wells, the swept area of which is shown in Figure 5.
  • the control electronics 27 can include a microcontroller to compute simple stop-go type operational signals from the chromatographic equipment 100 into the instructions necessary for stepper motor movements to provide correct dispenser positioning, and can provide feedback of the resting position of the dispenser and or a confirmation signal to a pump or valve of the equipment 100, to allow filling of the well when the dispenser is correctly positioned.
  • the illustrated orthogonal two dimensional array of wells is preferred, it is possible that other well patterns could be employed, with suitable alterations to the running of the electronics 27.
  • the wells could be arranged in staggered rows such that rounded wells can be closer together.
  • FIG. 8 is schematic, in that no details of any connecting or attaching means are shown. It is of course obvious for anyone skilled in the art that the components shown could be formed and assembled in numerous ways, each one selected to suit the application at hand, a more detailed example of that assembly being shown in Figure 6. Of course, the rotating movements shown could be transferred by any suitable means other than a belt transmission, such as a chain transmission, a gear transmission, a flexible drive shaft, or suitable four-bar linkages.
  • Figure 9 shows a base 20 having a central pedestal 40, privotably supporting an arm 30', along which can slide a liquid dispenser 35, fed by a capillary tube 36 for dispensing into collection microplates PI and P2, all as described above with reference to Figures 1 to 8.
  • this embodiment has a modified arm 30', including a central slot 70 in which the dispenser 35 travels in a driven linear manner in use.
  • Figure 10 shows the slot 70 in more detail.
  • the mechanism for moving the dispenser 35 along the arm 30 is similar to that described above, i.e.
  • the travel of the dispenser 35 can be increased if needed because the carriage is now smaller.
  • the dispenser is less likely to be knocked or damaged because it is protected in part inside the arm 30'.
  • a linear bearing is used to keep the dispenser in the correct position as described above, although in a lower cost version (not shown) it is possible that the slot 70 supports the dispenser 35 and carriage 34' without such a bearing.
  • the type of driving means for the arm 30 and carriage 34 such as DC motors with gear boxes, lever arms driven by linear movements from, for example a hydraulic or pneumatic cylinder or linear drives.

Landscapes

  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)

Abstract

L'invention concerne un collecteur de fraction permettant de distribuer des liquides dans plusieurs réceptacles (P1, P2) disposés en un réseau bidimensionnel. Le collecteur de fraction comprend une table (22) permettant de supporter lesdits réceptacles, et un bras maintenu au-dessus de la table, supportant à son tour un distributeur de liquide (35), le bras du collecteur de fraction pouvant pivoter autour d'un axe de bras (C) et le distributeur de liquide étant mobile le long du bras sur un chariot 34 (Figure 2). Ainsi, le distributeur est de faible coût et peut être repositionné simplement au-dessus des réceptacles en conséquence de ladite rotation et dudit mouvement le long du bras, sans occuper trop d'espace de travail de laboratoire.
PCT/EP2017/051867 2016-01-29 2017-01-27 Collecteur de fraction liquide pour système de chromatographie en phase liquide Ceased WO2017129802A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US16/070,846 US11333641B2 (en) 2016-01-29 2017-01-27 Liquid fraction collector for liquid chromatography system
CN201780008928.6A CN108496077B (zh) 2016-01-29 2017-01-27 用于液体色谱系统的液体馏分收集器
EP17701875.1A EP3408663B1 (fr) 2016-01-29 2017-01-27 Collecteur de fractions pour chromatographie en phase liquide
JP2018539405A JP7111615B2 (ja) 2016-01-29 2017-01-27 液体クロマトグラフィシステム用の液体フラクションコレクタ
US17/727,375 US11686712B2 (en) 2016-01-29 2022-04-22 Liquid fraction collector for liquid chromatography system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1601667.7A GB201601667D0 (en) 2016-01-29 2016-01-29 Improvements in and relating to liquid fraction collectors
GB1601667.7 2016-01-29

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US16/070,846 A-371-Of-International US11333641B2 (en) 2016-01-29 2017-01-27 Liquid fraction collector for liquid chromatography system
US17/727,375 Continuation US11686712B2 (en) 2016-01-29 2022-04-22 Liquid fraction collector for liquid chromatography system

Publications (1)

Publication Number Publication Date
WO2017129802A1 true WO2017129802A1 (fr) 2017-08-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2017/051867 Ceased WO2017129802A1 (fr) 2016-01-29 2017-01-27 Collecteur de fraction liquide pour système de chromatographie en phase liquide

Country Status (6)

Country Link
US (2) US11333641B2 (fr)
EP (1) EP3408663B1 (fr)
JP (1) JP7111615B2 (fr)
CN (1) CN108496077B (fr)
GB (1) GB201601667D0 (fr)
WO (1) WO2017129802A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201816610D0 (en) * 2018-10-11 2018-11-28 Ge Healthcare Bio Sciences Ab A fraction collection system and method
HUE071194T2 (hu) * 2019-05-31 2025-08-28 Genzyme Corp Kétdimenziós LC-MS/MS rendszerek
DE102019211885A1 (de) * 2019-08-08 2021-02-11 Syntegon Technology Gmbh Vorrichtung und Verfahren zum Handhaben von Behältern
JPWO2021038939A1 (fr) * 2019-08-23 2021-03-04
GB202013552D0 (en) * 2020-08-28 2020-10-14 Cytiva Sweden Ab Nozzle assembly for a fraction collection unit

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Publication number Priority date Publication date Assignee Title
US4077444A (en) * 1975-02-12 1978-03-07 Gilson Warren E Fraction collector
JPH0592717U (ja) * 1992-05-19 1993-12-17 武田薬品工業株式会社 フラクションコレクター
WO2000002038A1 (fr) * 1998-07-02 2000-01-13 Molecular Dynamics, Inc. Instrument robotise de bioanalyse d'echantillons dans les microcanaux
US20020104583A1 (en) * 2001-02-02 2002-08-08 Lars Andersson Fraction collector
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Also Published As

Publication number Publication date
JP2019503489A (ja) 2019-02-07
US11333641B2 (en) 2022-05-17
GB201601667D0 (en) 2016-03-16
US11686712B2 (en) 2023-06-27
CN108496077B (zh) 2021-12-21
JP7111615B2 (ja) 2022-08-02
EP3408663B1 (fr) 2024-06-12
US20220244227A1 (en) 2022-08-04
CN108496077A (zh) 2018-09-04
EP3408663A1 (fr) 2018-12-05
US20190064128A1 (en) 2019-02-28

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